Enhanced Activity of Ca2+-Activated K+ Channels by 1 2-Hydroxy-3-Propyl-4 - (1h-Tetrazol-5-Yl) Butoxyl Phenyl Ethanone (Ly-171883) in Neuroendocrine and Neuroblastoma Cell Lines
Resource
JOURNAL OF CELLULAR PHYSIOLOGY v.192 n.2 pp.188-199
Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Journal Volume
v.192
Journal Issue
n.2
Pages
188-199
Date Issued
2002
Date
2002
Author(s)
LIANG, JIN-TUNG
Abstract
The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH(3) and in neuroblastoma IMR-32 cells. In GH(3) cells, LY- 171883 (1-300 muM) reversibly increased the amplitude of Ca 2+-activated K+ current in a concentration-dependent manner with ail EC50 value of 15 muM. In excised indside-out patches recorded from CH3 cells, the application of LY- 171883 into cytosolic face did not modify single channel conductance of large-conductance Ca2+- activated K+ (BKCa) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BKCa channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 muM) suppressed the activity of BKCa channels and MK-571 (30 muM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 muM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH(3) cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 muM) also stimulated BKCa channel activity in a voltage-dependent manner. However, neither clofibrate (30 muM) nor leukotriene D-4 (10 muM) affected the channel activity in IMR-32 cells. Troglitazone (30 muM) decreased the channel activity, but ciglitazone (30 muM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BKCa channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function. (C) 2002 Wiley-Liss, Inc.
Subjects
ACTIVATED POTASSIUM CHANNELS
PITUITARY GH(3) CELLS
SMOOTH- MUSCLE CELLS
LARGE-CONDUCTANCE
GUINEA-PIG RAT
Type
journal article